1) Field of the Invention
This invention relates in general to biocompatible hydrophilic polymeric complexes. In one aspect this invention relates to biocompatible hydrophilic polymeric complexes which can be affixed to numerous substrates and therefore render them particularly useful for a variety of applications, particularly in the medical device, personal care, and health care fields. In a further aspect, the invention is directed to coated substrate materials wherein the substrate material may not itself be biocompatible, but since it possesses desirable physical and other properties, when coated with the polymeric complex it is then ideally suited for use in areas where biocompatibility is desired. In a still further aspect, this invention is directed to combinations of the complexes with biologically active agents, such as antimicrobial agents as well as to processes for their preparation.
2) Description of the Related Art
For many applications it is desirable to have a hydrophilic polymeric surface which is biocompatible with the animal and human body. However, many polymeric surfaces due to their chemical composition or method of preparation are not compatible with the body and hence they are not suitable for use in fields such as medical devices, personal care, health care, pharmaceuticals, and other areas of interest.
In addition, it is desirable that the hydrophilic polymer be firmly attached to the substrate such that it exhibits good abrasion resistance. Historically, techniques used to attach a polymer to a substrate include chemical treatment such as chemical cross-linking or exposure to a high energy radiation source, such as an electron beam machine. These methods are not usually desirable. A highly cross-linked composition prepared by any one of these techniques can often result in a different chemical composition from that of the parent polymer and therefore, such polymers might have a potentially different biological behavior. Furthermore, high-energy cross-linking often leads to polymer degradation and discoloration. Thus, the conventional cross-linking techniques are not particularly suited for preparing a polymeric coating from a biocompatible material since there is no assurance that the final coating will still possess the desired biocompatibility, physical properties, or both.
Of the many known natural and synthetic polymeric hydrophilic systems, two polymeric compounds are particularly noted for their biocompatibility and have found wide acceptance in a variety of areas where such biocompatibility is desired. One such known polymeric compound, poly(vinyl pyrrolidone), has an exceptionally low animal oral toxicity and a high parental lethal dose (LD.sub.50) and accordingly, has found extensive application in the pharmaceutical industry. For example, the United States Pharmacopeia, 22nd Revision, Jan. 1, 1990, discloses on page 1118 the product Povidone, which is a linear synthetic polymer consisting of poly(vinyl pyrrolidone). It is indicated that this polymer when complexed with iodine is useful as an ointment and as a topical anti-infective aerosol solution.
The biocompatibility of poly(vinyl pyrrolidone) is also mentioned in an article "Acetylene Derived Polymers", by S. C. Johnson, Comestics and Toiletries, Vol. 99, Jun. 14, 1984, pp 77-81.
A second well known class of polymeric compounds which are characterized by excellent biocompatibility with animals and humans, are the poly(ethylene oxides), particularly the high molecular weight ethylene oxide polymers. The biocompatibility of poly(ethylene oxide) with blood has been studied and reported in several journals, such as, for example, an article by George, J. N., Direct Assessment of Platelet Adhesion to Glass; study of the forces of interaction and the effects of plasma and serum factors, platelet function and modification of the glass surface, Blood, 40, 862, 1972.
Other articles include, Wasiewski, W., Rasio, M. J., Martin, B. M., Detwiler, J. C., and Fenton, J. W., Thrombin Absorption to Surfaces and prevention with PEG 6000, Thromb. Res., 8, 881, 1976, and S. W. Kim and J. feijen, "Critical Reviews in Biocompatibility", D. F. Williams, Editor, CRC Press, Inc., Boca Raton, Fla., Vol 1, issue 3, pp 229-260.
However, even though both poly(vinyl pyrrolidone) and poly(ethylene oxide) have excellent biocompatible properties with the human body, they do not readily adhere to substrates which might find application in the medical, personal care, health care, or pharmaceutical fields. Accordingly, prior to the present invention, substrates which are not normally biocompatible were rarely utilized in areas involving the human body even though they may possess desirable features of strength and mass which would otherwise render them suitable for such purposes.
A poly(lower-alkylene oxide) or a poly(N-vinyl lactam), such as poly(vinyl pyrrolidone), can be immobilized through complexation with a carboxylic acid-containing polymer on the surface of a variety of substrates forming an abrasion resistance, biocompatible coating. In some instances, the coatings also offer a high degree of lubricity in aqueous and body fluids such as blood. Since the complexes are formed through a relatively weak hydrogen bond or dipole-dipole interactions, the chemical compositions and properties of the parent polymer are largely preserved. Hence, the disadvantages of chemical cross-linking and other methods mentioned above are largely avoided. These biocompatible surfaces can be further formulated with additives, such as antimicrobial agents, to yield novel coated substrates having antimicrobial properties.
Accordingly, one or more of the following objects will be achieved by the practice of this invention. It is an object of this invention to provide biocompatible, polymeric abrasion resistant surfaces. Another object is to provide substrates coated with the polymeric complexes so that the outer exposed surface is biocompatible with its surrounding environment. A further object of this invention is to provide substrate materials, such as medical devices having a coating of a polymeric compound which is biocompatible. A further object is to provide substrates coated with the polymeric complexes and which contain additives such as antimicrobial agents and other pharmaceutically effective agents. A still further object of this invention is to provide processes for the preparation of the coated substrates. Another object is to provide medical and other devices and instruments which have a coating of a biocompatible material which becomes lubricious upon exposure to body fluids. These and other objects will readily become apparent to those skilled in the art in the light of the teachings herein set forth.